Editorial—Fistula Calprotectin as a Biomarker of Local Inflammation and Treatment Response in Perianal Fistulising Crohn's Disease. Authors' Reply

We appreciate Drs. Alsoudani and Swaminathan's thoughtful and constructive editorial, ‘Editorial—Fistula calprotectin as a biomarker of local inflammation and treatment response in perianal fistulising Crohn's disease’, in response to our recent study of fistula calprotectin (FiCP) as a biomarker for perianal fistulising Crohn's disease (pfCD) [1, 2]. Our study preliminarily demonstrates, in a single-centre cohort, that FiCP is a local inflammatory marker of fistulas and is associated with histological inflammation, clinical activity, imaging findings and treatment response, thereby providing a direct basis for its further clinical application [1]. This finding is also consistent with the growing demand for more precisely stratified and quantifiable biomarkers in the field of pfCD. Expert consensus has emphasised the urgent need for a more standardised hierarchical and clinical or trial decision-making framework for the disease [3]. In recent years, the study of quantitative imaging indicators such as MRI and fistula volume also reflects the development of ‘quantifiable, traceable and verifiable’ examination indicators in this field [4]. In this context, FiCP, which is directly derived from the local fistula microenvironment, may offer an advantage by more closely reflecting the inflammatory status of the fistula. Nevertheless, as pointed out by the two professors, FiCP should still be regarded as a research tool with potential transformation value [2]. Before entering clinical application, multicentre cohort verification is still needed to verify the stability of FiCP in different populations and clinical backgrounds. Secondly, the AGA clinical practise guidelines clearly state that there are variations between different detection methods for faecal calprotectin, and different kits or extraction processes also affect the results [5], suggesting the importance of establishing a standardised sampling and detection process. Recent studies have shown that surgical procedures can change the local environment and outcome of the fistula [6], therefore, patients receiving different surgical treatment strategies need to be included to dynamically evaluate the characteristics of FiCP changes. A multicentre study showed that the evaluation of pfCD should not only focus on short-term symptoms, but also on long-term imaging outcomes and clinical outcomes [7], FiCP reflects local inflammatory activity, and fistula healing is related to fibrosis remodelling. It will be valuable to explore the process of inflammation-fibrosis transformation by combining FiCP dynamic changes with imaging fibrosis indicators. Recent studies have also begun to emphasise the importance of the patient's perspective [8]. It is equally important to explore more minimally invasive or alternative sampling strategies for the systematic evaluation of patient acceptance and feasibility of fistula scraping sampling techniques. In summary, we agree with the views of Professors Alsoudani and Swaminathan. FiCP still needs to be further verified in larger samples, standardised processes and long-term follow-up studies, but this does not weaken its innovative value. FiCP represents a locally derived biomarker of fistula lesions that may reflect the local inflammatory state dynamically and could contribute to improved stratification and individualised monitoring in pfCD. Runqi Wang: writing – original draft. Dongxing Cao: writing – review and editing. Zhe Cui: conceptualization, writing – review and editing. The authors have nothing to report. The authors declarations of personal and financial interests are unchanged from those in the original article [1]. This article is linked to Wang et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70640 and https://doi.org/10.1111/apt.70600. The data that support the findings of this study are available from the corresponding author upon reasonable request.